Despite a wealth of new information on the pathophysiology and pharmacology of dementia syndromes, little progress has been made in our clinical understanding and management of these disease states. This is especially true of our understanding of the multiple synaptic effects of psychotropic medications in patients. Recent developments in our own laboratory as well as in others have made it possible to augment our clinical knowledge of dementia by means of drug level monitoring techniques which allow us to appreciate drug effects on multiple neurotrasmitter receptor systems. The proposed studies represent the first attempt to apply these recent advances in neurotransmitter receptor pharmacology and technology to patients with dementia syndromes. Using a double-blind cross-over design we will study the effects of two neuroleptic drugs on three subtypes of dementia (familial, sporatic, multi-infarct). The drugs will be haloperidol, a neuroleptic drug known to work principally at the DA2 receptor and with minimal anticholinergic effects, and thioridazine, a neuroleptic work at both DA1 and DA2 receptors and known to have substantial anticholinergic effects. The patients will be randomly assigned to treatment with each neuroleptic and dosages will be increased step-wise over the course of two to four months. Standard tests for memory, attention, motor side-effects, language and general functioning will be administered routinely and correlated with serum levels of neuroleptic and anticholinergic drugs as measured by radioreceptor assay techniques. The results of these studies should augment our current appreciation of the effect on neurotransmitter receptors of commonly employed drugs in the management of dementia. Findings from these studies should point to more detailed and elaborate studies in which drug receptor interactions in demented patients can be appreciated, particularly with regard to the integrity of the cholinergic nervous system. These findings will ultimately have broader implications both in terms of managing the clinical syndrome of dementia as well as generating effective markers for testing the integrity of specific receptor systems in patients who suffer with dementia.